Background: This study aimed to examine the effect of apigenin on proliferation and apoptosis in HER2-overexpressing MDA-MB-453 breast cancer cells.
Materials and methods: The antiproliferative effects of apigenin were examined by proliferation and MTT assays. The effect of apigenin on apoptotic molecules was determined by western blotting. RT-PCR was performed to measure mRNA levels of HIF-1α and VEGF. ELISA assay was performed to measure intracellular VEGF levels. Immunocytochemistry was performed to evaluate nuclear STAT3 level.
Results: Apigenin inhibited the proliferation of MDA-MB-453 cells. Apigenin up-regulated the levels of cleaved caspase-8 and caspase-3, and induced the cleavage of PARP. Apigenin induced extrinsic apoptosis and blocked the activation (phosphorylation) of JAK2 and STAT3. Apigenin inhibited CoCl2-induced VEGF secretion and decreased the nuclear staining of STAT3.
Conclusion: Apigenin exerts its antiproliferative activity by inhibiting STAT3 signaling. Apigenin could serve as a useful compound to prevent or treat HER2-overexpressing breast cancer.
Keywords: Breast cancer; HER2; STAT3; VEGF; apigenin; apotosis.
Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.